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The evaluation of in vitro activity of potentially antifungal compounds by microdilution broth method. VIII.
Kvítková, Lenka ; Buchta, Vladimír (advisor) ; Doležal, Martin (referee)
Kvítková L.: Evaluation of in vitro activity of potentially antifungal compounds by microdilution broth method - VIII. Over 250 new synthetized compounds divided into 16 chemical groups were tested by microdilution broth method for the establisment of in vitro antifungal activity. This method is based on the standard M27-A (Clinical Laboratory Standard Institute). RPMI 1640 medium buffered to pH 7.0 with MOPS was used and standardized inoculum was prepared from fresh fungal isolates grown on Sabouraud agar. All compounds tested were dissolved and diluted in DMSO. The MICs were determinated visually after 24 or 48 hours of incubation at 35C. The compounds were tested against eight fungal strains. The structure-activity relationships were studied and compared with the calculated log P values. Hydrophobicity of compounds (log P) was computed using the program ACD/LogP (Advanced Chemistry Development Inc., Ontario, Canada). The most active compounds were the derivatives of (E)-1-pyrazine-2- ylethane-1-one-thiosemicarbazone; the majority of the compounds showed moderate or high efficacy against all fungal strains tested. There were several compounds of the groups tested with a considerable antifungal effect, as well. The most susceptible fungal strain was Trichophyton mentagrophytes, on the contrary,...
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Synthesis of bisquaternary nonsymmetric acetylcholinesterase reactivators
Sopr, Stanislav ; Kopecký, Kamil (referee) ; Doležal, Martin (advisor)
Stanislav Sopr: PREPARATION OF BISQUARTERNARY NON-SYMETRIC ACETYLCHOLINESTERASE REACTIVATORS Abstract The acetylcholinesterase (AChE) reactivators cause the re-activation of AChE activity after inhibition by organophosphorus compounds (OP). Such OP inhibitors were formerly developed as pesticides, but they were further used as chemical warfare agents due to their extremely high inhibition of cholinesterases. In this diploma thesis, 18 novel AChE reactivators were prepared. Their ability to reactivate paraoxon-inhibited AChE was evaluated in vitro via Ellman's method and compared to 3 standard commercial compounds (pralidoxime, obidoxime and HI-6). Any newly prepared compound was superior to known standards at 10-4 mol/l concentration. However, three novel compounds were able to exceed reactivation ability of known standards at 10-6 mol/l concentration and one novel compound exceeded reactivation limit for further potential in vivo evaluation.
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Pyrazine derivates as potential drugs IV.
Loukotová, Veronika ; Zimčík, Petr (advisor) ; Doležal, Martin (referee)
Synthesis of unsymmetrical derivates of azaphthalocyanines I. Veronika Loukotová Department of Pharmaceutical Chemistry and Drug Control, Faculty of Pharmacy in Hradec Kralove, Charles University in Prague, Heyrovskeho 1203, Hradec Kralove, 50005, Czech Republic. Abstract: New metal free azaphthalocyanines (AzaPc) with unsymmetrical distribution of alkylamino substituents on periphery were prepared using a statistical approach of two different precursors, followed by chromatographic separation. Presence of bulky diethylamine substituents on periphery ensures very good monomerization in organic solvents and enabled simple separation of target AzaPc from statistical mixture. Diethylamine substitution was used therefore for precursor which formed ¾ of final AzaPc. An unsymmetrical part of macrocycle was then formed by precursors with 2-hydroxyethylamine- and 2-(2-hydroxyethoxy)ethylamine groups. Better yields were obtained from cyclization of AzaPc with long substituents on periphery compared to AzaPc with short peripheral substituents where many side products were observed on TLC. The reaction of free alcoholic group of prepared AzaPc with carboxylic group of similar molecule of AzaPc to form ester bond was undertaken but was not successful.
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Pyrazine derivates as potential drugs I.
Klusoňová, Petra ; Doležal, Martin (advisor) ; Opletalová, Veronika (referee)
Title of diploma thesis: Pyrazine derivatives as potential drugs I. Review of actual worldwide problem of tuberculosis and trends in the tuberculosis treatment and chemical recherché were the parts of this work. Novel pyrazine derivatives connected via -CONH- bridge with substituted anilines were synthesized. The synthetic approach, analytical, spectroscopic, lipophilicity and biological data of twelve newly synthesized compounds were presented. All products were characterized and tested against Mycobacterium tuberculosis strain H37Rv and against eight fungal pathogen strains. Additionally, the study of inhibition of oxygen evolution rate in spinach chloroplasts and reduction of chlorophyll content in the green algae Chlorella vulgaris in the series of prepared compounds were drawn. Structure-activity relationships among the chemical structure, lipophilicity (log P), and their biological activity of the evaluated compounds were discussed as well.
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Pyrazine derivates as potential drugs II.
Pagáčová, Jaroslava ; Doležal, Martin (advisor) ; Zimčík, Petr (referee)
Jaroslava Pagáčová: Pyrazine derivates as potential drugs II. Keywords : tuberculosis, Mycobacterium tuberculosis, Directly Observed Treatment Strategy, Multi drug Resistence, pyrazinoic acid, pyrazinamide, isoniazide, rifampicine, streptomycine, ethambutol Abstract of Diploma Thesis: This review is about worldwide problem of tuberculosis and about new trends in its treatment. Also chemical search about drugs and their preparing was done. The synthetic approach, analytical, spectroscopic, lipophilicity and biological data of twelve newly synthesized compounds were presented. Products were characterized and tested against Mycobacterium tuberculosis strain H37Rv and against eight fungal pathogen strains. Structure- activity relationships among the chemical structure, lipophilicity (log P), and their biological activity of the evaluated compounds were discussed as well.
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Pyrazine Derivates as Potential Antituberculotic Drugs
Kačírek, Michal ; Doležal, Martin (advisor) ; Kopecký, Kamil (referee)
Title of rigorous thesis: Pyrazine derivates as potential antituberculotic drugs Author: Mgr. Michal Kačírek In this rigorous thesis the recherche was realized which was focused on recent incidence of tuberculosis in the world, the possibility o f present therapy and the new trends in therapy as well. This thesis dealt with synthesis of undocumented compounds in literature. The starting compound was 5-chloro-6-methylpyrazine-2,3- dicabronitrile. The compounds were developed by aminodehalogenational reaction, linked to alkyl descriptor across amino group, whereas side chains were anal ogously extended. It can be said that the product was developed by reaction of 5 -chloro-6- methylpyrazine-2,3-dicabronitrile with corresponding primary aliphatic amine. Final compounds were characterized by thaw point, TLC, elementary analysis, 1 H a 13 C NMR and IR. All compounds were liable in vitro testing on their biological activity - antimycobacterial, antifungal and antibacterial. In the group of antituberculosis test ing the activity grew up from the least to the most lipophility compound.
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Derivates of 5-methylpyrazine-2-carboxylic Acid as Potential Drugs
Mistríková, Katarína ; Doležal, Martin (advisor) ; Vinšová, Jarmila (referee)
Title of rigorous thesis: Derivates of 5-methylpyrazine-2-carboxylic acid as potential drugs Introduction of rigorous thesis is about tuberculosis, its occurence in the world, drug resistence, pathogenesis, diagnosis, prevention and treatment, about used and developed drugs. Further, I describe methods of carboxylic acid amides preparation, schemes of reactions and six prepared anilides. These are characterized by melting temperature, elemental analysis, IR, 1 H and 13 C NMR spectroscopy. Synthetized compounds were tested in vitro for antituberculotic, antifungal and herbicidal activity. Also values of lipophilicity log P and log K were gained. Relationship between biological activity, chemical structure and lipophilicity of prepared substances was evaluated.
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Synthesis of Pyrazincarboxylic Acid Derivates as Potential
Sedlák, Petr ; Doležal, Martin (advisor) ; Kopecký, Kamil (referee)
Title of diploma thesis: Synthesis of pyrazincarboxylic acid derivates as potential antituberculotics Tuberculosis is a disease with about 9 million new cases every year, about 1,7 million people are dying yearly. For several decades the same antituberculotics are used for treatment, but new strains of tuberculosis are appearing and resistance is growing. The old antituberculotics become to be ineffective. There is need to be new ones researched. Review of tuberculosis therapy and modern research were presented in this thesis. Nine novel derivates of acylamine pyrazinic acid and its esters were synthesized. Novel structures were characterized by melting points, TLC, IR, 1H and 13C NMR. This set was put through in vitro biological evaluation. Log P and Clog P were also calculated and were compared with novel synthesized structures.
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The isolation of oligosacharides from cow' milk and their antiadhesive effects against Neisseria meningitidis
Kořínek, Michal ; Miletín, Miroslav (referee) ; Doležal, Martin (advisor)
Isolation of milk whey oligosaccharides and their anti-adhesion activity against Neisseria meningitidis Neisseria meningitidis is a human specific pathogen causing meningitis and septis. Meningococcal diseases are always very serious and can be fatal few hours after first symptoms are observed. Infants in the age of 6 to 12 months are in the highest risk to obtain meningococcal disease. Human and bovine milk oligosaccharides have been found to have inhibitory activity against several pathogens including Neisseria meningitidis. Anti-adhesive activity of acidic bovine milk whey oligosaccharides against Neisseria meningitidis was investigated in this study. Gel chromatography was used for fractination of the crude oligosaccharides isolated from bovine milk whey. The separated fractions were analyzed as regards acidic and neutral parts by measuring total hexoses and sialic acids content. The inhibitory activity of the specific acidic whey oligosaccharide fractions against the attachment of meningococcal pili was studied by using a solid-phase inhibition assay in vitro. Fractions of acidic whey oligosaccharides were found to inhibit adhesion of Neisseria meningitidis type IV pili proteins to bovine thyroglobulin that was used as a reference glycoprotein. Milk whey acidic oligosaccharides that have anti-adhesive...
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